Proteins that function in association with DNA have been extensively investigated in prokaryotic and eukaryotic systems because of their possible regulatory roles. We have used the technique of affinity chromatography on DNA-cellulose to isolate a class of DNA-binding proteins from human serum. These proteins appear to be unique among the serum proteins and comprise a significant fraction (1.5 percent) of these proteins. We propose to determine the physiological function(s) of the DNA-binding proteins by a combination of biochemical and clinical studies. Our first objective is to characterize the two major DNA-binding protein species in normal serum; these proteins have been purified to homogeneity. Their characterization includes: determination of physical and chemical properties by conventional techniques; determination of substrate specificity using a nitrocellulose membrane filter assay; determination of function including the use of an in vitro transcription system using human chromatin as template; development of radioimmunoassays for these proteins to facilitate the screen for genetic polymorphism in the general population. Our second objective is to continue the characterization of a malignancy-associated DNA-binding protein. This protein's characterization includes: determination of physical and chemical properties to explore its relationship to complement component C3; extensive use of a screening procedure and radioimmunoassay to definitively determine its potential as a prognostic and/or diagnostic indicator; exploration of the role of serum proteases in producing this protein and possibly others of the DNA-binding proteins. BIBLIOGRAPHIC REFERENCES: Parsons, R.L. and J.A. Hoch. 1976. A DNA-binding fragment of human complement component C3. Abstract submitted to Tenth International Congress of Biochemistry, Hamburg. McVey, E.B. and S.O. Hoch. 1976. The two major DNA-binding proteins in normal human serum. Abstract submitted to Tenth International Congress of Biochemistry, Hamburg.